The NF-κB pathway is a key regulator of inflammation, traditionally viewed as a proinflammatory signaling pathway. However, recent genetic studies in mice have revealed complex, dual roles for NF-κB in inflammation, suggesting both pro- and anti-inflammatory functions. NF-κB is involved in the expression of proinflammatory genes, including cytokines, chemokines, and adhesion molecules, but its role in inflammation is more nuanced than previously thought. The pathway has two main activation routes: the canonical pathway, which is triggered by proinflammatory cytokines and TLRs, and the alternative pathway, activated by specific cytokines and not by TNFα. The canonical pathway leads to the activation of RelA-containing complexes, while the alternative pathway activates RelB/p52 complexes. These pathways differ in their dependence on IKK subunits, with IKKβ regulating the canonical pathway and IKKα involved in the alternative pathway. NF-κB plays a critical role in inflammatory diseases, including chronic conditions like rheumatoid arthritis, inflammatory bowel disease, and asthma. However, its role is not straightforward, as it can also have anti-inflammatory effects, such as promoting apoptosis and inhibiting proinflammatory gene expression. Studies have shown that NF-κB can limit inflammation by promoting the resolution of inflammation and by regulating the balance between pro- and anti-inflammatory mediators. Additionally, NF-κB has been shown to influence the development of adaptive immunity, with the alternative pathway playing a role in lymphoid organogenesis and B-cell function. Recent research has highlighted the dual roles of NF-κB in inflammation and immunity, with the canonical pathway promoting inflammation and the alternative pathway contributing to immune regulation. The IKKα subunit has been shown to limit NF-κB activation during bacterial infection, promoting resolution of inflammation. However, NF-κB can also promote leukocyte apoptosis, which may contribute to the resolution of inflammation. These findings suggest that NF-κB is a complex and multifaceted pathway with both pro- and anti-inflammatory functions, making it a challenging but potentially important target for therapeutic intervention in inflammatory diseases.The NF-κB pathway is a key regulator of inflammation, traditionally viewed as a proinflammatory signaling pathway. However, recent genetic studies in mice have revealed complex, dual roles for NF-κB in inflammation, suggesting both pro- and anti-inflammatory functions. NF-κB is involved in the expression of proinflammatory genes, including cytokines, chemokines, and adhesion molecules, but its role in inflammation is more nuanced than previously thought. The pathway has two main activation routes: the canonical pathway, which is triggered by proinflammatory cytokines and TLRs, and the alternative pathway, activated by specific cytokines and not by TNFα. The canonical pathway leads to the activation of RelA-containing complexes, while the alternative pathway activates RelB/p52 complexes. These pathways differ in their dependence on IKK subunits, with IKKβ regulating the canonical pathway and IKKα involved in the alternative pathway. NF-κB plays a critical role in inflammatory diseases, including chronic conditions like rheumatoid arthritis, inflammatory bowel disease, and asthma. However, its role is not straightforward, as it can also have anti-inflammatory effects, such as promoting apoptosis and inhibiting proinflammatory gene expression. Studies have shown that NF-κB can limit inflammation by promoting the resolution of inflammation and by regulating the balance between pro- and anti-inflammatory mediators. Additionally, NF-κB has been shown to influence the development of adaptive immunity, with the alternative pathway playing a role in lymphoid organogenesis and B-cell function. Recent research has highlighted the dual roles of NF-κB in inflammation and immunity, with the canonical pathway promoting inflammation and the alternative pathway contributing to immune regulation. The IKKα subunit has been shown to limit NF-κB activation during bacterial infection, promoting resolution of inflammation. However, NF-κB can also promote leukocyte apoptosis, which may contribute to the resolution of inflammation. These findings suggest that NF-κB is a complex and multifaceted pathway with both pro- and anti-inflammatory functions, making it a challenging but potentially important target for therapeutic intervention in inflammatory diseases.